2-Chloroaniline → 5-(2-Chlorophenyl)aminomethyl-4-amino-2-methylthiopyrimidine

Participants

Reaction Conditions

Reaction Steps

A mixture of 4-amino-2-methylthiopyrimidine-5-carboxaldehyde (9.5 g, 56.1 mmol), 2-chloroaniline (6.7 mL, 63.7 mmol) and 4-toluene-sulfonic acid monohydrate (0.85 g, 4.5 mmol) in 350 mL of xylene was heated under reflux with azeotropic removal of water for 6 hours. The mixture was cooled to 25° C. and the precipitate was collected by vacuum filtration and was washed with hexanes and air dried. This solid was then dissolved in 300 mL tetrahydrofuran. and the reaction cooled to 0° C. Lithium aluminium hydride (2.3 g, 60.6 mmol) was added in small portions over 45 minutes. Once the addition was complete, the mixture was stirred for a further 15 minutes and carefully treated sequentially with 4.5 mL water, 4.5 mL of 15% aqueous sodium hydroxide and then 20 mL of water. The mixture was stirred for 30 minutes, filtered through celite, and the filtrate concentrated in vacuo. The solid was purified with column chromatography on silica gel using 25% acetone/hexane. The fractions containing product were concentrated under reduced pressure to a solid which was recrystallized from ethyl to give 7.0 g of 5-(2-chlorophenyl)aminomethyl-4-amino-2-methylthiopyrimidine as a white solid.

Provenance & Evidence